The world’s first CRISPR therapy is approved: who will receive it?

To date small number of patients can benefit from the first CRISPR therapy because of the high cost

Sickle cell disease and b-thalassemia are red blood cell disorders. In sickle cell disease hemoglobin is compromised and the unusual shape of red blood cells causes their adhesion to the capillaries, leading the blockage of the vessels and vasculo-occlusive crises. This condition requires blood transfusion and organ damage is elevated. The FDA has approved the first CRISPR-Cas9 gene editing therapy for Sickle cell disease and the approval for b-thalassemia will be on 30 March 2024.

CRISPR-Cas9 therapy eliminates severe vaso-occlusive crises typical in sickle cell disease

The Casgevy (exagamglogene autotemcel) is the first CRISPR-Cas9 therapy for sickle cell disease and b-thalassemia. In sickle cell disease it has the ability to compensate the loss of adult hemoglobin, that is due to a point mutation in the b -globin gene, but not fixing the mutation. Indeed, it has been designed to induce the production of fetal hemoglobin that usually is switched off after birth. The treatment eliminates severe vaso-occlusive crises that are typical of patients with sickle cell disease. However, to date the long-term safety profile of Casgevy is unknown but in the trial, participants showed no genotoxicity due to the therapy.

CRISPR therapy: how it works

Casgevy is the first CRISPR therapy approved in the world from the FDA. It is designed to induce fetal hemoglobin to compensate the loss of adult hemoglobin: the introduction of double-strand breaks in the DNA disrupts the expression of the BCL11A gene, thus inhibiting its repression activity on the transcription of the g-globulin. This novel strategy can transform the treatment and so the life of patients affected by these pathologies. However, this novel therapy is very expensive and to date it will be limited to few persons.

By Paola Brivio, Department of Pharmacological and Biomolecular Sciences, University of Milan

Link and doi of the pubblication; doi: 10.1038/d41587-023-00016-6